Abstract：
OBJECTIVE: To provide a comprehensive review of the pharmacokinetics, pharmacodynamics, safety, and efficacy of a new Food and Drug Administration (FDA) approved Bruton\'s tyrosine kinase inhibitor (BTKi), pirtobrutinib for relapsed/refractory mantle cell lymphoma (r/r MCL).
METHODS: A literature search was conducted through PubMed MEDLINE, ClinicalTrials.gov, and the FDA website (January 2018-January 2023) using the following key terms: lymphoma, non-covalent, Bruton\'s tyrosine kinase (BTK), and relapse. Relevant English language monographs, studies, and abstracts conducted in humans were reviewed and considered.
METHODS: Pirtobrutinib, a novel non-covalent BTKi, was granted accelerated approval for treatment of r/r MCL on January 27th, 2023, based on an open-label, multi-center phase 1/2 BRUIN trial. In phase l, 61 patients with r/r MCL received seven dose levels of pirtobrutinib (25-300 mg). There was no reported maximum tolerated dose or dose-limiting toxicities during this study period. In phase 2, 56 r/r MCL evaluable efficacy patients received pirtobrutinib 200 mg daily. The overall response rate (ORR) was 52% (95% CI 38-65). Additionally, patients who received a previous covalent BTKi, ORR was 52% (95% CI 38-66). Neutropenia was the most common adverse reaction reported as a grade 3 or higher.
CONCLUSIONS: Pirtobrutinib has demonstrated safety and efficacy in heavily pre-treated adult patients with r/r MCL. Advantages of this drug include its usage in patients whose malignancy is resistant to current BTKi, tolerability, and response rate. Multiple clinical trials are underway to determine the efficacy of pirtobrutinib in other B-cell malignancies.
METHODS: A literature search was conducted through PubMed MEDLINE, ClinicalTrials.gov, and the FDA website (January 2018-January 2023) using the following key terms: lymphoma, non-covalent, Bruton\'s tyrosine kinase (BTK), and relapse. Relevant English language monographs, studies, and abstracts conducted in humans were reviewed and considered.
METHODS: Pirtobrutinib, a novel non-covalent BTKi, was granted accelerated approval for treatment of r/r MCL on January 27th, 2023, based on an open-label, multi-center phase 1/2 BRUIN trial. In phase l, 61 patients with r/r MCL received seven dose levels of pirtobrutinib (25-300 mg). There was no reported maximum tolerated dose or dose-limiting toxicities during this study period. In phase 2, 56 r/r MCL evaluable efficacy patients received pirtobrutinib 200 mg daily. The overall response rate (ORR) was 52% (95% CI 38-65). Additionally, patients who received a previous covalent BTKi, ORR was 52% (95% CI 38-66). Neutropenia was the most common adverse reaction reported as a grade 3 or higher.
CONCLUSIONS: Pirtobrutinib has demonstrated safety and efficacy in heavily pre-treated adult patients with r/r MCL. Advantages of this drug include its usage in patients whose malignancy is resistant to current BTKi, tolerability, and response rate. Multiple clinical trials are underway to determine the efficacy of pirtobrutinib in other B-cell malignancies.
摘要：
目的：为全面审查药代动力学，药效学,安全,和新的食品和药物管理局（FDA）批准布鲁顿酪氨酸激酶抑制剂（BTKi）的疗效，吡托替尼治疗复发/难治性套细胞淋巴瘤（r/rMCL）。
方法：通过PubMedMEDLINE进行文献检索，ClinicalTrials.gov,和FDA网站（2018年1月至2023年1月）使用以下关键术语：淋巴瘤，非共价的,布鲁顿酪氨酸激酶（BTK），和复发。相关英文专著，研究,并对在人类中进行的摘要进行了审查和考虑。
方法：皮尔托布鲁替尼，一种新的非共价BTKi，1月27日获得r/rMCL治疗加速批准，2023年，基于开放标签，多中心1/2期BRUIN试验。在阶段l,61例r/rMCL患者接受了7个剂量水平的吡托布鲁替尼（25-300mg）。在该研究期间没有报告最大耐受剂量或剂量限制性毒性。在第2阶段，56例r/rMCL可评估疗效的患者每天接受吡托布鲁替尼200mg。总有效率（ORR）为52%（95%CI38-65）。此外,先前接受共价BTKi的患者，ORR为52%（95%CI38-66）。中性粒细胞减少症是最常见的不良反应，报告为3级或更高。
结论：Pirtobrutinib已证明在严重预处理的r/rMCL成年患者中具有安全性和有效性。该药物的优点包括其在恶性肿瘤对当前BTKi耐药的患者中的使用，耐受性,和回应率。多项临床试验正在进行中，以确定吡托替尼在其他B细胞恶性肿瘤中的疗效。
方法：通过PubMedMEDLINE进行文献检索，ClinicalTrials.gov,和FDA网站（2018年1月至2023年1月）使用以下关键术语：淋巴瘤，非共价的,布鲁顿酪氨酸激酶（BTK），和复发。相关英文专著，研究,并对在人类中进行的摘要进行了审查和考虑。
方法：皮尔托布鲁替尼，一种新的非共价BTKi，1月27日获得r/rMCL治疗加速批准，2023年，基于开放标签，多中心1/2期BRUIN试验。在阶段l,61例r/rMCL患者接受了7个剂量水平的吡托布鲁替尼（25-300mg）。在该研究期间没有报告最大耐受剂量或剂量限制性毒性。在第2阶段，56例r/rMCL可评估疗效的患者每天接受吡托布鲁替尼200mg。总有效率（ORR）为52%（95%CI38-65）。此外,先前接受共价BTKi的患者，ORR为52%（95%CI38-66）。中性粒细胞减少症是最常见的不良反应，报告为3级或更高。
结论：Pirtobrutinib已证明在严重预处理的r/rMCL成年患者中具有安全性和有效性。该药物的优点包括其在恶性肿瘤对当前BTKi耐药的患者中的使用，耐受性,和回应率。多项临床试验正在进行中，以确定吡托替尼在其他B细胞恶性肿瘤中的疗效。
